Immutep Limited announced the completion of patient enrollment in the TACTI-003 (KEYNOTE-PNC-34) Phase IIb trial evaluating eftilagimod alpha (efti), its proprietary soluble LAG-3 protein and MHC Class II agonist, in combination with MSD?s anti-PD-1 therapy KEYTRUDA ® (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The Phase IIb trial enrolled 171 patients at over 30 centres across the United States, Europe, and Australia to evaluate the safety and efficacy of efti in combination with pembrolizumab in patients with PD-L1 positive (Combined Positive Score [CPS] =1) tumors (Cohort A) and in patients with PD-L1 negative tumors (Cohort B). A total of 138 patients with recurrent or metastatic HNSCC whose tumours express PD-L1 (CPS =1) have been enrolled into the 1:1 randomized Cohort A of the trial evaluating the safety and efficacy of 30mg of efti in combination with 400mg of KEYTRUDA® given every six weeks compared to 400mg of KEYTRUDA® alone.

Patients in Cohort A whose tumors express PD-L1 (CPS >1) are also stratified by CPS 1-19 and CPS >20, and the clinical results for these three CPS groups will be evaluated. Additionally, 33 patients with recurrent or metastatic HNSCC were enrolled into Cohort B to determine the efficacy and safety of the same combination therapy in patients with PD-L1 negative tumours (CPS <1). These patients are not expected to respond to KEYTRUDA® monotherapy, with a typical Overall Response Rate of up to 5%, and therefore were not randomized.1 Due to a higher number of patients with negative PD-L1 expression (CPS <1) who were eligible for and allocated to Cohort B and the number of patients in screening at the time of achieving the trial?s enrollment goal, the trial enrolled 171 patients.

The primary endpoint of the study is Overall Response Rate of evaluable patients according to RECIST 1.1. Secondary endpoints include Overall Survival, Overall Response Rate according to iRECIST, Progression Free Survival, and Duration of Response. The primary analysis according to the trial protocol will be performed after all subjects have completed at least three cycles of treatment (18 weeks in total) or discontinued the trial, and all relevant data for the primary endpoint has been collected, cleaned, and analysed. The Company expects to report data from the trial in H1 CY2024.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer by incidence worldwide, with 890,000 new cases and 450,000 deaths reported in 2018.2,3,4 It is an aggressive, genetically complex, and difficult to treat cancer. 5 Furthermore, HNSCC is associated with high levels of psychological distress and compromised quality of life (QOL).6 As such, HNSCC patients need improved treatment options. Eftilagimod alpha was granted Fast Track designation by the FDA in April 2021 for treatment of first-line HNSCC.

For more information about the Phase IIb trial, visit clinicaltrials.gov (NCT04811027).